Biomedical Engineering Reference
In-Depth Information
cardiovascular toxicity of CNTs. Tang et al.
18
demonstrated no significant and acute toxicities from
CNTs to the heart when mice were intravenously injected with 100 μg of either short (s)-MWCNTs
or polyethylene glycol (PEG)-modified ones (s-MWCNTs-PEG) as indicated by histological exami-
nation and blood levels of creatine kinase, an indicator of heart damage. Another study describing
the use of functionalized MWCNTs as ultrasound contrast agents showed that IV injections of
MWCNTs did not exert adverse effects on the heart by histological examination or the analysis of
blood.
19
It should be noted that some blood parameters may be altered upon CNT treatments, which
might be due to the effect of CNTs on other organs. For example, the level of aspartate transami-
nase (AST) in mouse blood was elevated when mice were intravenously injected with pristine (p)
and acid-oxidized (f) MWCNTs with varying degrees of carboxylation. In addition, p-MWCNTs
induced the highest level of AST because they showed the highest propensity of liver accumulation
and caused maximum liver damage in mice.
20
A few
in vitro
studies using cell models have been carried out to examine the potential effects of
CNTs on the cardiovascular system. Cheng et al.
21
found that SWCNT exposure induced oxidative
damage in rat aortic endothelial cells (RAECs), suggesting potential adverse effects on the car-
diovascular system. It was additionally found that the expression levels of the stress protein, heme
oxygenase-1 (HO-1), increased with the increasing concentration of SWCNTs. Contrarily, however,
when Martinelli et al.
22
cultured neonatal rat ventricular myocytes (NRVMs) with MWCNT scaf-
folds, they observed the increased viability and proliferation of these NRVMs. Furthermore, altera-
tions in the electrophysiological properties of cardiomyocytes suggest the ability of MWCNTs to
promote cardiomyocyte maturation.
22
12.2.1.2 Graphene
Since the first single layers of graphene were identified in 2004 by Geim and coworkers,
23
graphene
family materials, including graphene, graphene oxide, and reduced graphene oxide, have attracted
a considerable interest, both in the academic and industrial fields. So far, the toxicity studies of
graphene family materials are still in their infancy, with even less literature regarding their cardio-
vascular toxicity.
By using a zebrafish model, Gollavelli and Ling
24
found that 0.1 ng/nL of graphene oxide and its
functionalized counterpart (polyacrylic acid [PAA] and fluorescein
o
-methacrylate [FMA]-modified
magnetic graphene oxide) induced 2% and 6% cardiac malfunction, respectively. In another study,
Duch et al.
25
compared the effects of graphene and graphene oxide on mouse lungs 24 h after pul-
monary instillation. Through histological examination, graphene oxide was found to induce severe
lung inflammation, while graphene, either dispersed or aggregated, showed minimal lung inflam-
mation. The authors pointed out the potentially increased risk of heart attacks and stroke following
lung inflammation.
12.2.2 s
IlIca
N
aNoMaterIals
Naturally occurring silica-based materials, such as asbestos and silica, have been investigated as
air pollutants for many years. On the other hand, synthetic amorphous silica nanoparticles (SNPs),
including the recently developed mesoporous silica nanoparticles (MSNs), are gaining an increasing
popularity as the material of choice in the biomedical and biotechnological fields as drug carriers,
for gene therapy, and for molecular imaging. SNPs are generally recognized as low toxic; thus, they
were approved as a food additive by Food and Drug Administration (FDA),
26
and used as a low-
toxic reference material in cytotoxicity experiments.
27
In this section, we will focus on the cardio-
vascular toxicity of synthetic silica nanomaterials.
The biomedical applications of SNPs as diagnostic, imaging, and drug-delivery agents were
often achieved via IV administration; thus, most of the
in vivo
toxicity studies were performed
through this administration route, including the studies for cardiovascular toxicity. The SNPs
were relatively biocompatible with the cardiovascular system in terms of both acute and chronic
